Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening

Vinoth, Kumar Jayaseelan and Manikandan, Jayapal and Sethu, Swaminathan and Balakrishan, Lakshmidevi and Heng, Alexis Boon Chin * and Lu, Kai and Hande, Manoor Prakash and Cao, Tong (2014) Evaluation of human embryonic stem cells and their differentiatedfibroblastic progenies as cellular models for in vitro genotoxicity screening. Journal of Biotechnology, 184. pp. 154-168. ISSN 0168-1656

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Abstract

This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progeniesas cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic progenies (H1F) displayed significantly higher chromosomal aberrations, micronuclei formation and double strand break (DSB) formation, as compared toundifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL, both of which are representative of somatic cell types commonly used for genotoxicity screening. Subsequently, transcriptomic and pathways analysis identified differential expression of critical genes involved in cell death and DNA damage response upon exposure to gamma irradiation. The results thus demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly-used somatic cell types for genotoxicity screening. Moreover, hESCs have additional advantages, such as their genetic normality compared to immortalized cell lines, as well as their amenability to scale-up for producing large, standardized quantities of cells for genotoxicity screening on an industrial scale, something which can never be achieved with primary cell cultures.

Item Type: Article
Additional Information: Fifth author, Alexis Heng, is with the Dept. of Biological Sciences, Faculty of Science and Technology, Sunway University.
Uncontrolled Keywords: Differentiation; DNA; microarray; mitomycin C; Oxidative; radiation; repair; stress
Subjects: Q Science > QR Microbiology
Divisions: Sunway University > School of Science and Technology > Dept. Biological Sciences
Depositing User: Ms. Molly Chuah
Date Deposited: 02 Apr 2015 02:01
Last Modified: 02 Apr 2015 02:01
URI: http://eprints.sunway.edu.my/id/eprint/265

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